While normal T cells are an integral part of mammalian immune response, in some instances it is desirable to inhibit undesirable immune responses such as undesirable proliferation of T cells. For instance, autoimmune diseases are characterized as an immune reaction against "self" antigens. Autoimmune diseases include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS). SLE and RA have previously been treated with anti-inflammatory/immunosuppressive drugs such as steroids or anti-inflammatory drugs in combination with immunosuppressive drugs. No effective treatment has previously been found for MS although ACTH and other immunosuppressive drugs have elicited some degree of response when administered during relapse. Inhibition of the undesired immune response, such as those associated with RA, SLE and MS would be greatly desired to combat these conditions. T cells are an integral part of the immune response. Thus, treatment directed to inhibition of T cell proliferation would be greatly desired to treat such undesired immune responses.
T cells have also been implicated in graft rejection and graft versus host disease (GVHD). Administration of immunosuppression drugs such as cyclosporin is one method which is presently used in an attempt to combat graft rejection. GVHD has previously been treated by depleting T cells from the donor bone marrow. As in cases of autoimmune diseases, the undesired immune response may be targeted at the T cell level to reduce rejection of transplanted organs and prevent the recognition by transplanted T cells of a host organism as "foreign".
Furthermore, abnormal T cell growth associated with T cell leukemias may be treated by inhibiting the proliferation of T cells. Patients suffering from leukemias have low survival rates and are generally treated with chemotherapy. Methods directed toward the undesired proliferation of T cells may be useful for treatment of such leukemias.
There is a need for new compounds and methods for treating: autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS); graft rejection and graft versus host disease (GVHD) and T cell leukemias. There is a need for new compounds and methods directed to the inhibition of undesirable immune responses such as the undesired proliferation of T cells.